{"entity":{"id":"her2-low","kind":"term","name":"HER2-low and HER2-ultralow","aka":["HER2-low","HER2 low","HER2-ultralow","HER2 ultralow","HER2-ultra-low","HER2 IHC 1+","IHC 1+","IHC 2+ ISH-negative","HER2 IHC 0","HER2-zero","HER2 0","HER2 immunohistochemistry score","HER2-low status"],"tldr":"Tumours with a little HER2 (IHC 1+ or 2+ without amplification), or a trace (ultralow), which older HER2 drugs ignored but Enhertu can attack.","summary":"HER2-low describes tumours with a little HER2, scored IHC 1+ or 2+ without gene amplification, and HER2-ultralow describes a trace, scored IHC 0 with faint membrane staining in a small fraction of cells. Older HER2 drugs ignored these tumours, but Trastuzumab deruxtecan can attack them, as DESTINY-Breast04 and DESTINY-Breast06 showed in HR-positive / HER2-negative breast cancer and Triple-negative breast cancer (TNBC). The result redefined what 'HER2-negative' means and put pressure on pathology to score the low end reliably, hence the links to Histopathology & immunohistochemistry, Companion diagnostics, the pairing HER2-low scoring to T-DXd and the idea on AI quantification of HER2-low. It also appears in the bottleneck on biomarker validation and the Giuseppe Curigliano entry.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/HER2","links":[{"label":"NCI Dictionary of Cancer Terms: HER2-low breast cancer","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/her2-low-breast-cancer"},{"label":"Quinn et al., Histopathology 2026;89(2):199 to 218: World Health Organization classification of tumours of the breast, 6th edition 2026","url":"https://doi.org/10.1111/his.70149"}],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-testing-uk-breast","who-breast-classification"],"trials":["destiny-breast04","destiny-breast06"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The classification has caught up with the drugs. The sixth edition of the WHO Classification of Tumours of the Breast (April 2026) updates the HER2 reporting categories after DESTINY-Breast04 and DESTINY-Breast06, making the distinction between no membrane staining at all and any membrane staining a reporting requirement rather than a research nicety, because that boundary now decides eligibility for trastuzumab deruxtecan (Quinn 2026)."],"category":"Biomarkers"},"route":"/terms/her2-low/","neighbours":{"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"her2-low-metastatic-breast-cancer","kind":"cancer","name":"HER2-low and HER2-ultralow metastatic breast cancer","route":"/cancers/her2-low-metastatic-breast-cancer/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"drug":[{"id":"her2-testing-assays","kind":"drug","name":"HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)","route":"/drugs/her2-testing-assays/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"term":[{"id":"amplification","kind":"term","name":"Amplification","route":"/terms/amplification/"},{"id":"er-pr-negative-threshold","kind":"term","name":"ER and PR negative under 1 percent (the triple-negative threshold, and ER-low)","route":"/terms/er-pr-negative-threshold/"},{"id":"her2-testing-uk-breast","kind":"term","name":"HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP","route":"/terms/her2-testing-uk-breast/"},{"id":"her2-low-and-trop2-adc-eligibility-tnbc","kind":"term","name":"HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)","route":"/terms/her2-low-and-trop2-adc-eligibility-tnbc/"},{"id":"her2-positive","kind":"term","name":"HER2-positive (IHC 3+ or ISH-amplified)","route":"/terms/her2-positive/"},{"id":"overexpression","kind":"term","name":"Overexpression","route":"/terms/overexpression/"},{"id":"receptor-conversion-breast","kind":"term","name":"Receptor conversion: when the receptors change between the primary and a recurrence","route":"/terms/receptor-conversion-breast/"},{"id":"who-breast-classification","kind":"term","name":"The WHO classification of breast tumours, and what the 6th edition changed","route":"/terms/who-breast-classification/"}],"trial":[{"id":"destiny-breast04","kind":"trial","name":"DESTINY-Breast04","route":"/trials/destiny-breast04/"},{"id":"destiny-breast06","kind":"trial","name":"DESTINY-Breast06","route":"/trials/destiny-breast06/"}],"paper":[{"id":"paper-denkert-her2-low-pooled-neoadjuvant-lancet-oncol-2021","kind":"paper","name":"Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials","route":"/key-papers/paper-denkert-her2-low-pooled-neoadjuvant-lancet-oncol-2021/"},{"id":"paper-schettini-her2-low-features-npj-breast-cancer-2021","kind":"paper","name":"Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer","route":"/key-papers/paper-schettini-her2-low-features-npj-breast-cancer-2021/"},{"id":"paper-destiny-breast04-nejm-2022","kind":"paper","name":"DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group","route":"/key-papers/paper-destiny-breast04-nejm-2022/"},{"id":"paper-destiny-breast06-nejm-2024","kind":"paper","name":"DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer","route":"/key-papers/paper-destiny-breast06-nejm-2024/"},{"id":"paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026","kind":"paper","name":"Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status","route":"/key-papers/paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"idea":[{"id":"idea-tnbc-adc-sequencing-trial","kind":"idea","name":"A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer","route":"/ideas/idea-tnbc-adc-sequencing-trial/"},{"id":"idea-ai-her2-low-scoring","kind":"idea","name":"AI quantification of HER2-low and HER2-ultralow","route":"/ideas/idea-ai-her2-low-scoring/"},{"id":"idea-tr2-her2-low-reference-materials","kind":"idea","name":"Calibrated reference slides so every lab scores HER2-low the same way","route":"/ideas/idea-tr2-her2-low-reference-materials/"},{"id":"idea-tr2-biomarker-negative-arms","kind":"idea","name":"Randomised trials to test whether biomarker-negative patients really do not benefit","route":"/ideas/idea-tr2-biomarker-negative-arms/"},{"id":"idea-bio1-rebiopsy-before-switch","kind":"idea","name":"Re-test the metastasis, not the old primary, before every change of treatment","route":"/ideas/idea-bio1-rebiopsy-before-switch/"},{"id":"idea-tnbc-her2-ultralow-testing-uptake","kind":"idea","name":"Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan","route":"/ideas/idea-tnbc-her2-ultralow-testing-uptake/"},{"id":"idea-tr2-marker-stratified-default","kind":"idea","name":"Test the drug in biomarker-negative patients too, so the biomarker can be validated","route":"/ideas/idea-tr2-marker-stratified-default/"}],"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"pairing":[{"id":"her2-low-to-tdxd","kind":"pairing","name":"HER2-low scoring → T-DXd","route":"/pairings/her2-low-to-tdxd/"}],"person":[{"id":"giuseppe-curigliano","kind":"person","name":"Giuseppe Curigliano","route":"/people/giuseppe-curigliano/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-knowledge-diffusion","kind":"bottleneck","name":"Knowledge reaches practice too slowly","route":"/bottlenecks/b-knowledge-diffusion/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"biomarker":[{"id":"her2-ihc-0","kind":"biomarker","name":"HER2 IHC 0 (HER2-negative, including ultralow)","route":"/biomarkers/her2-ihc-0/"},{"id":"her2-ihc-1-plus","kind":"biomarker","name":"HER2 IHC 1+","route":"/biomarkers/her2-ihc-1-plus/"},{"id":"her2-ihc-2-plus","kind":"biomarker","name":"HER2 IHC 2+ (equivocal, reflex to ISH)","route":"/biomarkers/her2-ihc-2-plus/"},{"id":"her2-low-ihc","kind":"biomarker","name":"HER2-low (IHC 1+ or IHC 2+/ISH-negative)","route":"/biomarkers/her2-low-ihc/"},{"id":"her2-ultralow","kind":"biomarker","name":"HER2-ultralow (IHC 0 with membrane staining)","route":"/biomarkers/her2-ultralow/"},{"id":"trop2-expression","kind":"biomarker","name":"TROP2 expression","route":"/biomarkers/trop2-expression/"}]}}